FI2968461T3 - Fusion proteins comprising pdgf and vegf binding portions and methods of using thereof - Google Patents

Fusion proteins comprising pdgf and vegf binding portions and methods of using thereof Download PDF

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FI2968461T3
FI2968461T3 FIEP14722439.8T FI14722439T FI2968461T3 FI 2968461 T3 FI2968461 T3 FI 2968461T3 FI 14722439 T FI14722439 T FI 14722439T FI 2968461 T3 FI2968461 T3 FI 2968461T3
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fusion protein
seq
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amino acid
acid sequence
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Peter Pechan
Jeffery Ardinger
Hillard Rubin
Samuel Wadsworth
Abraham Scaria
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    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
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    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

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Claims (17)

PATENTTIVAATIMUKSETPATENT CLAIMS 1. Fuusioproteiini, joka käsittää (a) veri- hiutaleperäisen kasvutekijän reseptori beetan (PDGFRB) ekstrasellulaarisen osan, joka käsittää PDGFRB:n Ig:n kaltaiset domeenit D1 - D3, (kb) vaskulaarisen endoteli- aalisen kasvutekijän (VEGF) reseptorin ekstrasellulaa- risen osan ja (c) multimerisaatiodomeenin, joka käsittää IgGl-vasta-aineen Fc-alueen, jossa fuusioproteiini si- toutuu PDGF:ään ja VEGF:ään, jossa fuusioproteiini on järjestetty N-päästä C-päähän seuraavassa järjestyk- sessä: (a), (b) ja (c), jossa fuusioproteiini käsittää linkkeripeptidin (a):n ja (b):n välissä käsittäen Sero:n (SEKV. ID NO: 49), jossa fuusioproteiini käsittää link- kerin (b):n ja (c):n välissä käsittäen Glyo:n (SEKV. ID NO: 47), ja jossa VEGF-reseptorin ekstrasellulaarinen osa koostuu Ig:n kaltaisesta domeenista D2.1. A fusion protein comprising (a) the extracellular portion of the platelet-derived growth factor receptor beta (PDGFRB) comprising the Ig-like domains D1 to D3 of PDGFRB, (kb) the extracellular portion of the vascular endothelial growth factor (VEGF) receptor part and (c) a multimerization domain comprising the Fc region of an IgG1 antibody in which the fusion protein binds to PDGF and VEGF, wherein the fusion protein is arranged from N-terminus to C-terminus in the following order: (a), (b) and (c), wherein the fusion protein comprises a linker peptide between (a) and (b) comprising Sero (SEQ ID NO: 49), wherein the fusion protein comprises linker (b) and ( c), comprising Glyo (SEQ ID NO: 47), and wherein the extracellular portion of the VEGF receptor consists of the Ig-like domain D2. 2. Patenttivaatimuksen 1 mukainen fuusioprote- iini, jossa PDGFR:n ekstrasellulaarinen osa käsittää: (a) PDGFRB:n Ig:n kaltaiset domeenit D1 - D5; (b) aminohapposekvenssin, jonka identtisyys SEKV. ID NO: 1:n tai 3:n kanssa on vähintään 85 %; tai (c) aminohapposekvenssin SEKV. ID NO: 1 tai 3.2. The fusion protein according to claim 1, wherein the extracellular part of PDGFR comprises: (a) the Ig-like domains D1 to D5 of PDGFRB; (b) an amino acid sequence having identity to SEQ. ID NO: with 1 or 3 is at least 85%; or (c) an amino acid sequence SEQ. ID NO: 1 or 3. 3. Patenttivaatimuksen 1 tai patenttivaatimuk- sen 2 mukainen fuusioproteiini, jossa VEGF-reseptorin ekstrasellulaarinen osa käsittää: (a) aminohapposekvenssin, jonka identtisyys SEKV. ID NO: 4:n kanssa on vähintään 85 %; tai (b) SEKV. ID NO: 4:n mukaisen aminohapposek- venssin.3. The fusion protein according to claim 1 or claim 2, wherein the extracellular part of the VEGF receptor comprises: (a) an amino acid sequence whose identity is SEQ. ID NO: with 4 is at least 85%; or (b) SEQ. The amino acid sequence according to ID NO: 4. 4. Jonkin patenttivaatimuksista 1 - 3 mukainen fuusioproteiini, jossa multimerisaatiodomeeni käsittää: (a) aminohapposekvenssin, jonka identtisyys SEKV. ID NO: 6:n kanssa on vähintään 85 %; tai (b) SEKV. ID NO: 6:n mukaisen aminohapposek- —venssin.4. The fusion protein according to one of claims 1 to 3, wherein the multimerization domain comprises: (a) an amino acid sequence whose identity is SEQ. ID NO: with 6 is at least 85%; or (b) SEQ. of the amino acid sequence of ID NO: 6. 5. Jonkin patenttivaatimuksista 1 - 4 mukainen fuusioproteiini, jossa fuusioproteiini käsittää SEKV.5. A fusion protein according to one of claims 1 to 4, wherein the fusion protein comprises SEQ. ID NO: 13:n, 15:n, 43:n tai 45:n mukaisen aminohapposek- venssin, tai aminohapposekvenssin, jonka identtisyys SEKV. ID NO: 13:n, 15:n, 43:n tai 45:n kanssa on vähin- tään 85 %.The amino acid sequence according to ID NO: 13, 15, 43 or 45, or the amino acid sequence whose identity SEQ. ID NO: with 13, 15, 43 or 45 is at least 85%. 6. Jonkin patenttivaatimuksista 1 - 5 mukainen fuusioproteiini, jossa fuusioproteiini on dimeerisessä tai multimeerisessä muodossa.6. The fusion protein according to one of claims 1 to 5, wherein the fusion protein is in dimeric or multimeric form. 7. Koostumus, joka käsittää jonkin patentti- vaatimuksista 1 - 6 mukaisen fuusioproteiinin ja farma- seuttisesti hyväksyttävän kantajan.7. A composition comprising a fusion protein according to one of claims 1 to 6 and a pharmaceutically acceptable carrier. 8. Nukleiinihappo, joka koodaa jonkin patent- tivaatimuksista 1 - 5 mukaista fuusioproteiinia.8. Nucleic acid encoding a fusion protein according to one of claims 1 to 5. 9. Isäntäsolu, joka käsittää nukleotidisek- venssin, joka koodaa jonkin patenttivaatimuksista 1 - 5 mukaista fuusioproteiinia.9. A host cell comprising a nucleotide sequence encoding a fusion protein according to one of claims 1 to 5. 10. Menetelmä fuusioproteiinin valmista- miseksi, joka menetelmä käsittää isäntäsolun, joka kä- sittää nukleiinihapon, joka koodaa jonkin patenttivaa- timuksista 1 - 5 mukaista fuusioproteiinia, viljelyn olosuhteessa, joka tuottaa fuusioproteiinia, ja isän- täsolun tuottaman fuusioproteiinin talteenottamisen.10. A method for producing a fusion protein, which method comprises culturing a host cell comprising a nucleic acid encoding a fusion protein according to one of claims 1 to 5, which produces a fusion protein, and recovering the fusion protein produced by the host cell. 11. Jonkin patenttivaatimuksen 1 - 6 mukainen fuusioproteiini käytettäväksi menetelmässä sairauden hoitamiseksi subjektilla, jossa menetelmä käsittää vai- kuttavan määrän fuusioproteiinia antamisen subjektille.11. A fusion protein according to one of claims 1 to 6 for use in a method for treating a disease in a subject, wherein the method comprises administering an effective amount of fusion protein to the subject. 12. Fuusioproteiini käytettäväksi patenttivaa- timuksen 11 mukaisesti, jossa subjektilla on makula- rappeuma, kostea silmänpohjan ikärappeuma, kuiva sil- mänpohjan ikärappeuma, proliferatiivinen diabeettinen retinopatia, syöpä, reumatoidiartriitti, os- teoartriitti, astma, uveiitti tai sarveiskalvon neovas- kularisaatio, ja jossa fuusioproteiini annetaan valin- naisesti intravitreaalisella injektiolla subjektille.12. A fusion protein for use according to claim 11 in which the subject has macular degeneration, wet macular degeneration, dry macular degeneration, proliferative diabetic retinopathy, cancer, rheumatoid arthritis, osteoarthritis, asthma, uveitis or corneal neovascularization, and in which the fusion protein is optionally administered by intravitreal injection to the subject. 13. Vektori, joka käsittää nukleotidisekvens- sin, joka koodaa jonkin patenttivaatimuksista 1 - 5 mu- kaista fuusioproteiinia.13. A vector comprising a nucleotide sequence encoding a fusion protein according to one of claims 1 to 5. 14. Rekombinanttinen adenoassosioitu virusvek- tori (rAAV) -partikkeli, joka käsittää nukleiinihapon, joka koodaa jonkin patenttivaatimuksista 1 - 5 mukaista fuusioproteiinia.14. A recombinant adeno-associated virus vector (rAAV) particle comprising a nucleic acid encoding a fusion protein according to one of claims 1 to 5. 15. Menetelmä TAAV-partikkelin valmista- miseksi, joka menetelmä käsittää: (a) isäntäsolun viljelyn olosuhteessa, jossa valmistuu rAAV-partikkeleita, jossa isäntäsolu käsittää (i) yhden tai useampia AAV-pakkausgeenejä, jossa kukin mainittu AAV-pakkausgeeni koodaa AAV-replikaatio- tai kapselointiproteiinia; (ii) rAAV-pro-vektorin, joka kä- sittää nukleotidin, joka koodaa jonkin patenttivaati- muksista 1 - 5 mukaista fuusioproteiinia, jota vähintään yksi AAV:n ITR reunustaa, ja (iii) AAV-auttajafunktion; ja (b) isäntäsolun tuottamien rAAV-partikkelien talteenottamisen.15. A method for producing a TAAV particle, which method comprises: (a) culturing a host cell under conditions in which rAAV particles are produced, wherein the host cell comprises (i) one or more AAV packaging genes, wherein each of said AAV packaging genes encodes AAV replication - or an encapsulation protein; (ii) an rAAV pro-vector comprising a nucleotide encoding a fusion protein according to one of claims 1 to 5 flanked by at least one AAV ITR, and (iii) an AAV helper function; and (b) recovering rAAV particles produced by the host cell. 16. Patenttivaatimuksen 14 mukainen rAAV-par- tikkeli käytettäväksi menetelmässä sairauden hoita- miseksi subjektilla, jossa menetelmä käsittää vaikutta- van määrän rAAV-partikkelia antamisen subjektille.16. The rAAV particle according to claim 14 for use in a method for treating a disease in a subject, wherein the method comprises administering an effective amount of rAAV particle to the subject. 17. rAAV-partikkeli käytettäväksi patenttivaa- timuksen 16 mukaisesti, jossa subjektilla on makula- rappeuma, kostea silmänpohjan ikärappeuma, kuiva sil- mänpohjan ikärappeuma, proliferatiivinen diabeettinen retinopatia, syöpä, reumatoidiartriitti, os- teoartriitti, astma, uveiitti tai sarveiskalvon neovas- kularisaatio, ja jossa rAAV-partikkeli annetaan valin- naisesti intravitreaalisella injektiolla subjektille.17. rAAV particle for use according to claim 16, where the subject has macular degeneration, wet macular degeneration, dry macular degeneration, proliferative diabetic retinopathy, cancer, rheumatoid arthritis, osteoarthritis, asthma, uveitis or corneal neovascularization, and wherein the rAAV particle is optionally administered by intravitreal injection to the subject.
FIEP14722439.8T 2013-03-13 2014-03-13 Fusion proteins comprising pdgf and vegf binding portions and methods of using thereof FI2968461T3 (en)

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